The early-stage NSCLC comes with challenges and limited treatment options. OPDIVO + chemotherapy is approved in the US and several other countries as a neoadjuvant therapy for adult patients with resectable NSCLC (tumors > 4 cm or node-positive) and in the EU as a neoadjuvant therapy for patients with resectable NSCLC at high risk of recurrence and with tumor PD-L1 expression > 1%. Exploring a perioperative strategy involving additional adjuvant OPDIVO holds the potential to further decrease the risk of disease recurrence and enhance clinical outcomes in resectable NSCLC patients. 

CheckMate 77T is a Phase III randomized, double-blind, placebo-controlled, multicenter trial evaluating neoadjuvant OPDIVO with chemotherapy followed by surgery and adjuvant OPDIVO vs. neoadjuvant chemotherapy and placebo followed by surgery and adjuvant placebo in 452 patients with resectable stage IIA to IIIB NSCLC. The primary endpoint of the trial is event-free survival (EFS). Secondary endpoints include overall survival (OS), pathologic complete response (pCR), and major pathologic response (MPR).

With a median follow-up of 25.4 months, in patients treated with neoadjuvant OPDIVO and chemotherapy followed by surgery and adjuvant OPDIVO, the risk of disease recurrence, progression, or death was reduced by 42%. Additionally, neoadjuvant OPDIVO and chemotherapy showed improvements in the secondary efficacy endpoints of pCR and MPR. The study is ongoing to assess its other secondary endpoint, i.e.,  OS. Definitive surgery rates were 78% with the OPDIVO-based regimen vs. 77% with chemotherapy and placebo, with complete resection achieved in 89% vs. 90% of patients, respectively. Furthermore, the safety profile of the perioperative OPDIVO-based regimen remained consistent, and surgical feasibility was similar between treatment arms. CheckMate 77T stands as the first Phase III perioperative study to build upon the established standard of care involving neoadjuvant OPDIVO + chemotherapy, reaffirming the potential of perioperative OPDIVO as a promising new treatment option for patients with resectable NSCLC. These findings represent a significant advancement in the management of this condition, offering improved outcomes and hope for patients.

KOL insights

“CheckMate 77T: a phase III trial of neoadjuvant nivolumab (or placebo) + chemotherapy, surgery, then adjuvant nivolumab or placebo for 1 year. Primary endpoint EFS (BICR). Median f/u here 25.4 months (9/2023 data lock)” - Director of Thoracic Oncology & Developmental Therapeutics, Lombardi Comprehensive Cancer Center, US

Conclusion

So far, OPDIVO has demonstrated improved efficacy in the neoadjuvant, adjuvant, or perioperative management of four distinct cancer types, including lung cancer, bladder cancer, esophageal/gastroesophageal junction cancer, and melanoma. The combination of neoadjuvant OPDIVO with chemotherapy followed by surgery and adjuvant OPDIVO has shown significant and clinical improvement in EFS when compared to chemotherapy/placebo in patients with resectable NSCLC. This improvement was consistent across various patient subgroups, indicating its broad applicability. Notably, the rates of pCR and MPR were substantially improved with the neoadjuvant OPDIVO-based regimen, highlighting its effectiveness in reducing tumor burden. Additionally, an exploratory analysis revealed that perioperative OPDIVO favored EFS, especially in patients achieving a PCR following neoadjuvant therapy, with a positive trend in patients without a PCR.

Although OPDIVO achieved a significant milestone by obtaining approval in March 2022 as the primary neoadjuvant treatment for early-stage NSCLC, its dominance was short-lived. In October 2023, KEYTRUDA became the first PD-1 inhibitor to secure approval for both pre-surgery and post-surgery treatment in resectable NSCLC, which has raised questions about OPDIVO's impact on the market. Other players like AstraZeneca have reported positive Early EFS results for IMFINZI in the perioperative context through the AEGEAN trial, which is promising; however, it is still too early to expect regulatory support. Meanwhile, Roche's TECENTRIQ has experienced delays in its IMpower-030 trial, with results now expected in 2024.

NSCLC accounts for up to 85% of lung cancer. DelveInsight estimates that the total incident population of NSCLC in the 7MM will reach nearly 600,000 in 2032. Estimates show that the highest incident population of NSCLC is in the United States followed by Japan, Germany, and the UK. 

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to the Non-Small Cell Lung Cancer (NSCLC) Market Insight and Forecast Report.

Note: The therapeutics segment is experiencing significant NSCLC clinical trial activity, which is further expected to drive Non-Small Cell Lung Caner market growth in the coming years.